A chloroplast-derived C4V3 polypeptide from the human immunodeficiency virus (HIV) is orally immunogenic in mice

Rubio-Infante, Néstor; Govea‐Alonso, Dania O.; Alpuche-Solís, Ángel G.; García‐Hernández, Ana Lilia; Soria-Guerra, Ruth Elena; Paz-Maldonado, Luz María Teresita; Ilhuicatzi-Alvarado, Damaris; Varona-Santos, Javier T.; Verdín-Terán, Leticia; Korban, Schuyler S.; Moreno‐Fierros, Leticia; Rosales‐Mendoza, Sergio

doi:10.1007/s11103-011-9870-1

Cited by 35 publications

(10 citation statements)

References 34 publications

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“…The synthetic C4V3 peptide, which includes the C4 domain and the V3 loop from HIV gp120, was introduced into tobacco chloroplasts and expressed at up to 25 μg/g FW in the leaves. Plant‐derived C4V3 elicited both mucosal and systemic immune responses, but the antibody titres were not quantified; CD4 + T‐cell proliferation responses were observed (Rubio‐Infante et al ., ). A lettuce‐based C4(V3)6 multi‐epitopic protein within the V3 loops, corresponding to five different HIV isolates including CC, MN, IIIB, RF and RU, elicited local and systemic immune responses when orally delivered to BALB/c mice.…”

Section: Illustrative Examples Of Plant‐based Vaccines Against Human mentioning

confidence: 97%

Plant‐made oral vaccines against human infectious diseases—Are we there yet?

Chan

Daniell

2015

Plant Biotechnology Journal

129

131

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Summary Although the plant-made vaccine field started three decades ago with the promise of developing low-cost vaccines to prevent infectious disease outbreaks and epidemics around the globe, this goal has not yet been achieved. Plants offer several major advantages in vaccine generation, including low-cost production by eliminating expensive fermentation and purification systems, sterile delivery and cold storage/transportation. Most importantly, oral vaccination using plant-made antigens confers both mucosal (IgA) and systemic (IgG) immunity. Studies in the past 5 years have made significant progress in expressing vaccine antigens in edible leaves (especially lettuce), processing leaves or seeds through lyophilization and achieving antigen stability and efficacy after prolonged storage at ambient temperatures. Bioencapsulation of antigens in plant cells protects them from the digestive system; the fusion of antigens to transmucosal carriers enhances efficiency of their delivery to the immune system and facilitates successful development of plant vaccines as oral boosters. However, the lack of oral priming approaches diminishes these advantages because purified antigens, cold storage/transportation and limited shelf life are still major challenges for priming with adjuvants and for antigen delivery by injection. Yet another challenge is the risk of inducing tolerance without priming the host immune system. Therefore, mechanistic aspects of these two opposing processes (antibody production or suppression) are discussed in this review. In addition, we summarize recent progress made in oral delivery of vaccine antigens expressed in plant cells via the chloroplast or nuclear genomes and potential challenges in achieving immunity against infectious diseases using cold-chain-free vaccine delivery approaches.

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Section: Illustrative Examples Of Plant‐based Vaccines Against Human mentioning

confidence: 97%

Plant‐made oral vaccines against human infectious diseases—Are we there yet?

Chan

Daniell

2015

Plant Biotechnology Journal

129

131

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“…In this study, LipY was not fused to CTB. Oral delivery of plant cells expressing subunit vaccine candidates, without fusion to CTB has been shown to elicit immunogenic response and/or confer protection against pathogen challenge [29], [47]–[49]. Therefore, LipY was first expressed without CTB fusion but future studies will consider using CTB fusion.…”

Section: Methodsmentioning

confidence: 99%

Low Cost Tuberculosis Vaccine Antigens in Capsules: Expression in Chloroplasts, Bio-Encapsulation, Stability and Functional Evaluation In Vitro

et al. 2013

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Tuberculosis (TB) caused by Mycobacterium tuberculosis is one of the leading fatal infectious diseases. The development of TB vaccines has been recognized as a major public health priority by the World Health Organization. In this study, three candidate antigens, ESAT-6 (6kDa early secretory antigenic target) and Mtb72F (a fusion polyprotein from two TB antigens, Mtb32 and Mtb39) fused with cholera toxin B-subunit (CTB) and LipY (a cell wall protein) were expressed in tobacco and/or lettuce chloroplasts to facilitate bioencapsulation/oral delivery. Site-specific transgene integration into the chloroplast genome was confirmed by Southern blot analysis. In transplastomic leaves, CTB fusion proteins existed in soluble monomeric or multimeric forms of expected sizes and their expression levels varied depending upon the developmental stage and time of leaf harvest, with the highest-level of accumulation in mature leaves harvested at 6PM. The CTB-ESAT6 and CTB-Mtb72F expression levels reached up to 7.5% and 1.2% of total soluble protein respectively in mature tobacco leaves. Transplastomic CTB-ESAT6 lettuce plants accumulated up to 0.75% of total leaf protein. Western blot analysis of lyophilized lettuce leaves stored at room temperature for up to six months showed that the CTB-ESAT6 fusion protein was stable and preserved proper folding, disulfide bonds and assembly into pentamers for prolonged periods. Also, antigen concentration per gram of leaf tissue was increased 22 fold after lyophilization. Hemolysis assay with purified CTB-ESAT6 protein showed partial hemolysis of red blood cells and confirmed functionality of the ESAT-6 antigen. GM1-binding assay demonstrated that the CTB-ESAT6 fusion protein formed pentamers to bind with the GM1-ganglioside receptor. The expression of functional Mycobacterium tuberculosis antigens in transplastomic plants should facilitate development of a cost-effective and orally deliverable TB booster vaccine with potential for long-term storage at room temperature. To our knowledge, this is the first report of expression of TB vaccine antigens in chloroplasts.

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“…Potato [28] Lettuce [29] Maize [30] Human Immunodeficiency Virus (HIV) p24-Nef, C4V3, Multi-HIV Tobacco [31][32][33] C4(V3)6 multi-epitopic protein Lettuce [34] p24…”

Section: Hepatitis B Surface Antigen (Hbsag)mentioning

confidence: 99%

Emergence of Novel Coronavirus 2019-nCoV: Need for Rapid Vaccine and Biologics Development

2020

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Novel Coronavirus (2019-nCoV) is an emerging pathogen that was first identified in Wuhan, China in late December 2019. This virus is responsible for the ongoing outbreak that causes severe respiratory illness and pneumonia-like infection in humans. Due to the increasing number of cases in China and outside China, the WHO declared coronavirus as a global health emergency. Nearly 35,000 cases were reported and at least 24 other countries or territories have reported coronavirus cases as early on as February. Inter-human transmission was reported in a few countries, including the United States. Neither an effective anti-viral nor a vaccine is currently available to treat this infection. As the virus is a newly emerging pathogen, many questions remain unanswered regarding the virus's reservoirs, pathogenesis, transmissibility, and much more is unknown. The collaborative efforts of researchers are needed to fill the knowledge gaps about this new virus, to develop the proper diagnostic tools, and effective treatment to combat this infection. Recent advancements in plant biotechnology proved that plants have the ability to produce vaccines or biopharmaceuticals rapidly in a short time. In this review, the outbreak of 2019-nCoV in China, the need for rapid vaccine development, and the potential of a plant system for biopharmaceutical development are discussed.

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A chloroplast-derived C4V3 polypeptide from the human immunodeficiency virus (HIV) is orally immunogenic in mice

Cited by 35 publications

References 34 publications

Plant‐made oral vaccines against human infectious diseases—Are we there yet?

Plant‐made oral vaccines against human infectious diseases—Are we there yet?

Low Cost Tuberculosis Vaccine Antigens in Capsules: Expression in Chloroplasts, Bio-Encapsulation, Stability and Functional Evaluation In Vitro

Emergence of Novel Coronavirus 2019-nCoV: Need for Rapid Vaccine and Biologics Development

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